1. GRIGNARD REAGENTS AND REACTIONS
Rayat Shikshan Sanstha's
S.M. JOSHI COLLEGE, HADAPSAR, PUNE-28
A SEMINAR ON
GRIGNARD REAGENTS AND REACTIONS
Prof. MADHURI TUPE (Assistant Professor)
Department of Chemistry 1

2. Grignard reagents act as nucleophiles toward the carbonyl group
diethyl ether d+ R C d– R
MgX C + O O ••
• •
MgX
• • •• –
H3O+ •• R C OH
• •
two-step sequence gives an alcohol as the isolated product 23

3. Grignard reagents react with:
formaldehyde to give primary alcohols aldehydes to give secondary alcohols ketones to give tertiary alcohols esters to give tertiary alcohols 3

4. Grignard reagents react with:
formaldehyde to give primary alcohols 3

5. Grignard reagents react with formaldehyde
diethyl ether d+ R C d– R
MgX H C
MgX + O O ••
• •
• • •• –
H3O+ H •• R C OH
• •
product is a primary alcohol H 23

6. Example Mg Cl
MgCl
diethyl ether C O H
H3O+
CH2OH
CH2OMgCl
(64-69%) 5

7. Grignard reagents react with:
formaldehyde to give primary alcohols aldehydes to give secondary alcohols 3

8. Grignard reagents react with aldehydes
diethyl ether d+ R C d– R
MgX R' C
MgX + O O ••
• •
• • •• –
H3O+ H •• R C OH
• •
product is a secondary alcohol R' 23

9. Example Mg CH3(CH2)4CH2Br CH3(CH2)4CH2MgBr diethyl ether C O H3C H
H3O+
CH3(CH2)4CH2CHCH3 OH
CH3(CH2)4CH2CHCH3
OMgBr
(84%) 5

10. Grignard reagents react with:
formaldehyde to give primary alcohols aldehydes to give secondary alcohols ketones to give tertiary alcohols 3

11. Grignard reagents react with ketones
diethyl ether d+ R C d– R
MgX R' C
MgX + O O ••
• •
• • •• –
H3O+
R" •• R C OH
• •
product is a tertiary alcohol R' 23

12. Example Mg
CH3Cl
CH3MgCl
diethyl ether O
CH3 HO
CH3
ClMgO
H3O+
(62%) 5

13. 14.7 Synthesis of Alcohols Using Organolithium Reagents
Organolithium reagents react with aldehydes and ketones in the same way that Grignard reagents do. 10

14. Example CH O +
H2C
CHLi
1. diethyl ether
2. H3O+
CH2
CHCH OH
(76%) 5

15. 14.8 Synthesis of Acetylenic Alcohols12

16. Using Sodium Salts of Acetylenes
NaNH2 HC CH HC
CNa
NH3 O HO C CH
1. NH3 HC
CNa +
2. H3O+
(65-75%) 13

17. Using Acetylenic Grignard ReagentsCH
CH3(CH2)3C +
CH3CH2MgBr
diethyl ether
CMgBr
CH3(CH2)3C +
CH3CH3
1. H2C O
2. H3O+
CCH2OH
CH3(CH2)3C
(82%) 13

18. 14.9 Retrosynthetic Analysis
Retrosynthetic analysis is the process by which we plan a synthesis by reasoning backward from the desired product (the "target molecule"). 14

19. Retrosynthetic Analysis of Alcohols
Step 1 Locate the carbon that bears the hydroxyl group. 15

20. Retrosynthetic Analysis of Alcohols
Step 2 Disconnect one of the groups attached to this carbon. 15

21. Retrosynthetic Analysis of Alcohols15

22. Retrosynthetic Analysis of Alcohols
MgX C O
What remains is the combination of Grignard reagent and carbonyl compound that can be used to prepare the alcohol. 15

23. There are two other possibilities. Can you see them?
Example C OH
CH3
CH2CH3
There are two other possibilities. Can you see them?
CH3MgX C
CH2CH3 O 20

24. Synthesis Mg, diethyl ether CH3Br CH3MgBr C CH2CH3 O 1. 2. H3O+ C OH21

25. 14.10 Preparation of Tertiary Alcohols From Esters and Grignard Reagents24

26. Grignard reagents react with esters
OCH3 •• R'
diethyl ether d+ R C
OCH3 •• d– R
MgX C + O O ••
• •
MgX
• • •• –
but species formed is unstable and dissociates under the reaction conditions to form a ketone 23

27. Grignard reagents react with esters
OCH3 •• R'
diethyl ether d+ R C
OCH3 •• d– R
MgX C + O O ••
• •
MgX
• • •• –
–CH3OMgX
this ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol C O R R'
• • •• 23

28. Example O + 2 CH3MgBr (CH3)2CHCOCH3 1. diethyl ether 2. H3O+
Two of the groups attached to the tertiary carbon come from the Grignard reagent OH
(CH3)2CHCCH3
CH3
(73%) 26

29. THANK YOU 26